1,3-Difluorobenzene → tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate

HRID 1773683ノート

反応式

HRID 1773683 の反応式
[Li]CCCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.[CH3:14][C:15]1[C:19]([C:20]2[CH:21]=[C:22]([CH:39]=[O:40])[C:23]3[N:27]=[C:26]([O:28][CH2:29][CH3:30])[N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:24]=3[CH:38]=2)=[C:18]([CH3:41])[O:17][N:16]=1>C1COCC1>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[C:39]([C:22]1[C:23]2[N:27]=[C:26]([O:28][CH2:29][CH3:30])[N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:32])[C:24]=2[CH:38]=[C:20]([C:19]2[C:15]([CH3:14])=[N:16][O:17][C:18]=2[CH3:41])[CH:21]=1)=[O:40]

参加物

5

反応物 3

HCID 97411,3-DifluorobenzeneHCID 117601313tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-benzo[d]imidazole-1-carboxylateHCID 178418339Butyllithium

生成物 1

HCID 117601789tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

n-BuLi (0.58 mL, 0.93 mmol) was added dropwise to a solution of 1,3-difluorobenzene (0.102 mL, 0.1 mmol) in THF (5 mL) cooled to −78° C. and allowed to stir for 1 hour. tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-benzo[d]imidazole-1-carboxylate (200 mg, 0.52 mmol) in THF was added and the reaction was allowed to stir for 5 mins at −78° C., quenched with ammonium chloride, extracted with EtOAc and concentrated. The crude was then taken up in DCM (2 mL), Des-Martin periodinane (290 mg, 0.78 mmol) was added and the reaction was allowed to stir for 15 mins. The reaction was quenched with sat. Na2S2O3, extracted with EtOAc, concentrated and purified by silica gel chromatography to give tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate.

後処理

  1. stirringto stir for 5 mins at −78° C.
  2. customquenched with ammonium chloride
  3. extractionextracted with EtOAc
  4. concentrationconcentrated
  5. additionDes-Martin periodinane (290 mg, 0.78 mmol) was added
  6. stirringto stir for 15 mins
  7. customThe reaction was quenched with sat. Na2S2O3
  8. extractionextracted with EtOAc
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography

出典と根拠

ORDレコード
ord-b4b93425df404970b1120659a84e7342
出典データセット
uspto-grants-2016_02
特許番号
US09255089B2

反応ノート

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